Protease-containing liquid detergent compositions are well known. A commonly encountered problem, particularly with heavy duty liquid laundry detergents, is the degradation by proteolytic enzyme of second (non-protease) enzymes in the composition, such as lipase, amylase and cellulase or combinations thereof. The performance of the second enzyme upon storage, and its stability in product are thus impaired by proteolytic enzyme.
Boronic acids are known to reversibly inhibit proteolytic enzyme activity. This inhibition is reversible upon dilution, as occurs when a laundry detergent containing the enzyme is dissolved in the preparation of laundry wash water.
The inhibition constant (Ki) is ordinarily used as a measure of capacity to inhibit enzyme activity, with a low Ki indicating a more potent inhibitor. However, it has been found that not all boronic acids are sufficiently effective inhibitors of proteolytic enzyme in liquid detergents, particularly heavy duty liquid laundry detergents, regardless of their Ki values. This is believed to be due to a base catalyzed decomposition of the boronic acid caused by the alkaline medium of a heavy duty liquid, with the extent and rate of the decomposition being dependent on the structure of the boronic acid molecule.
A discussion of the inhibition of one proteolytic enzyme, subtilisin, is provided in Philipp, M. and Bender, M. L., "Kinetics of Subtilisin and Thiolsubtilisin", Molecular & Cellular Biochemistry, vol. 51, pp. 5-32 (1983). Inhibition constants for boronic acids are provided therein, and boronic acids are cited as subtilisin inhibitors. Low Ki values are said to indicate more effective inhibitors.
One class of boronic acid, peptide alkylboronic acid, is discussed as an inhibitor of trypsin-like serine proteases such as thrombin, plasma kallikrein and plasmin, especially in pharmaceuticals, in European Patent Application 0 293 881, Kettner et al., published Dec. 7, 1988.
European Patent Application Ser. No. 90/870212, published Nov. 14, 1990 discloses liquid detergent compositions containing certain bacterial serine proteases and lipases.
U.S. Pat. No. 4,908,150, Hessel et al, issued Mar. 13, 1990 describes liquid detergent compositions containing lipolytic enzymes wherein the stability of the lipolytic enzyme is said to be improved by inclusion of particular nonionic ethylene glycol containing copolymers.
U.S. Pat. No. 4,566,985, Bruno et al, issued Jan. 28, 1986 describes liquid cleaning compositions containing a mixture of enzymes including a protease and second enzymes. The composition also contains an effective amount of benzamidine hydrohalide to inhibit the digestive effect of protease on the second enzymes. The inhibition effect is reversed upon dilution.
In European Application 0 376 705, Cardinali et al, published Jul. 4, 1990, liquid detergent compositions containing a mixture of lipolytic enzymes and proteolytic enzymes have been described. The storage stability of the lipolytic enzyme is said to be enhanced by the inclusion of a lower aliphatic alcohol and a salt of a lower carboxylic acid and a surfactant system which is predominantly nonionic.
In European Patent Application 0 381 262 Aronson et al, published Aug. 8, 1990, mixtures of proteolytic and lipolytic enzymes in a liquid medium have been disclosed. The stability of lipolytic enzyme is said to be improved by the addition of a stabilizing system comprising boron compound and a polyol which are capable of reacting, whereby the polyol has a first binding constant with the boron compound of at least 500 l/mole and a second binding constant of at least 1000 l.sup.2 /mole.sup.2.
PCT Application WO 92/19707, published Oct. 30, 1992 discloses meta substituted boronic acids as reversible protease inhibitors in liquid laundry detergents. They are indicated as being superior to the para substituted isomers for this purpose.
The stability of several substituted phenylboronic acids is discussed by Kuivila et al. in Canadian Journal of Chemistry at 3081-3090 (1963).